Depression, one of the most common diseases in older adults, carries significant risk for morbidity, and mortality. However, many older adults with depression are not identified, and even when identified, they face protracted courses of treatment, with nearly two-thirds of elderly patients failing to achieve symptomatic remission. Given the burgeoning population of older adults, as well as the enormous burden of depression, efforts to maximize depression prevention are needed. Prior history of depression is a robust risk predictor of depression in older adults. Furthermore, we have found that sleep disturbance is prospectively associated with depression recurrence in older adults independent of other depressive symptoms, as well as antidepressant and hypnotic medication use. In this study, we hypothesize that recognition and treatment of sleep disturbance, a modifiable behavioral risk factor, will prevent depression recurrence in older adults who have a history of depression. In addition, because increasing evidence also implicates inflammation as a biological mechanism that contributes to depression, we further hypothesize that increases in inflammation are associated with the link between sleep disturbance and depression recurrence. The over-arching objective of this proposal is to evaluate the ability of a behavioral intervention, cognitive behavioral therapy for sleep quality (CBT-SQ) to reduce sleep complaints, depression recurrence, and cellular and genomic markers of inflammation in older adults with sleep complaints who have a prior history of depression. In this select and targeted older adult population, we aim to: 1) evaluate the effects of CBT-SQ vs. Sleep Seminar (SS) on objective (actigraphy) and subjective (sleep diary; questionnaire) measures of sleep symptoms over a two-year follow-up; 2) determine the effects of CBT-SQ vs. SS on recurrence of depressive symptoms and depression episode(s) over a two-year follow-up. We will also secondarily examine the effects of CBT-SQ vs. SS on cellular and genomic markers of inflammation over a two-year follow-up, and explore whether markers of inflammation and cytokine genetic polymorphisms explain variability in the risk of depression recurrence in those older adults receiving CBT-SQ vs. SS. This study is highly significant and innovative by focusing on prevention, rather than treatment, of depression in older adults; identifying a high risk group that takes into account both non-modifiable (i.e., prior history of depression) and modifiable (i.e., sleep disturbance) risk factors; using an intervention that specifically targets a modifiable risk factor (i.e., sleep disturbance) with implications for trial efficiency and efficacy; and examining a biological risk factor (i.e., inflammation), which has the potential to inform understanding of the pathways that contribute to depression and its prevention. PUBLIC HEALTH RELEVANCE: Depression in the elderly is a major public health concern. Indeed, as the population ages in high-income countries, depression is projected to increase by 2030 to a position of the greatest contributor to illness burden. Moreover, because elderly persons with depression often do not receive diagnosis and treatment, and only about one-third of depressed older adults achieve remission using current treatment approaches, over two-thirds of the disease burden remains intact leading to staggering costs in the health care sector. The present study is highly significant by being the first study, to our knowledge, to focus on the prevention of depression in community dwelling older adults who have a history of depression, and by targeting sleep disturbance, a modifiable risk factor to prevent depression recurrence.